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PKCε‐mediated P‐Rex1 downregulation suppresses breast cancer cell proliferation
Author(s) -
Wong ChuuYun A.,
Xie Yan,
Wolff Dennis W.,
Abel Peter W.,
Tu Yaping
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1096.10
Subject(s) - rex1 , protein kinase c , cell growth , downregulation and upregulation , cancer research , breast cancer , cancer cell , signal transduction , biology , cancer , medicine , microbiology and biotechnology , embryonic stem cell , biochemistry , induced pluripotent stem cell , gene
P‐Rex1, a Rac1 selective activator, is upregulated and promotes tumorgenesis and metastasis of various cancers. We recently found that phorbol‐12‐myristate‐13‐acetate (PMA) downregulates P‐Rex1 in breast cancer cells. The present study was to investigate the importance and mechanism underlying PMA downregulation of P‐Rex1. P‐Rex1 mRNA and protein expression were determined by real‐time RT‐PCR and Western blot analysis, respectively. Cell proliferation was analyzed by counting cell numbers. We found that P‐Rex1 expression is elevated in breast cancer MCF‐7, T47D and BT‐474 cell lines compared to normal breast epithelial cells. PMA treatment decreased P‐Rex1 expression and proliferation of breast cancer cells by over 70%. Restoring P‐Rex1 expression attenuated the PMA inhibition of cell proliferation. Go6983, a protein kinase C (PKC) inhibitor, blocked the PMA inhibition of P‐Rex1 expression and breast cancer cell proliferation. Breast cancer cells express PMA‐sensitive PKCδ, PKCε and PKCη. Overexpression of constitutively active PKCε, but not PKCδ or PKCη, significantly suppressed P‐Rex1 expression and breast cancer cell proliferation. In conclusion, PMA downregulates P‐Rex1 to suppress breast cancer cell proliferation via a PKCε signaling pathway, which could be a new therapeutic target for development of a novel breast cancer treatment. Supported by NIH CA125661 and Nebraska State LB595.